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Opposing Roles of apolipoprotein E in aging and neurodegeneration.
Hudry, Eloise; Klickstein, Jacob; Cannavo, Claudia; Jackson, Rosemary; Muzikansky, Alona; Gandhi, Sheetal; Urick, David; Sargent, Taylie; Wrobleski, Lauren; Roe, Allyson D; Hou, Steven S; Kuchibhotla, Kishore V; Betensky, Rebecca A; Spires-Jones, Tara; Hyman, Bradley T.
Afiliação
  • Hudry E; Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA ehudry@mgh.harvard.edu.
  • Klickstein J; Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
  • Cannavo C; Centre for Discovery Brain Sciences, UK Dementia Research Institute, and Edinburgh Neuroscience, The University of Edinburgh, Edinburgh, UK.
  • Jackson R; Centre for Discovery Brain Sciences, UK Dementia Research Institute, and Edinburgh Neuroscience, The University of Edinburgh, Edinburgh, UK.
  • Muzikansky A; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Gandhi S; Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
  • Urick D; Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
  • Sargent T; Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
  • Wrobleski L; Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
  • Roe AD; Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
  • Hou SS; Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
  • Kuchibhotla KV; Johns Hopkins University, Baltimore, MD, USA.
  • Betensky RA; Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
  • Spires-Jones T; Centre for Discovery Brain Sciences, UK Dementia Research Institute, and Edinburgh Neuroscience, The University of Edinburgh, Edinburgh, UK.
  • Hyman BT; Alzheimer Research Unit, Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA.
Life Sci Alliance ; 2(1)2019 02.
Article em En | MEDLINE | ID: mdl-30760557
Apolipoprotein E (APOE) effects on brain function remain controversial. Removal of APOE not only impairs cognitive functions but also reduces neuritic amyloid plaques in mouse models of Alzheimer's disease (AD). Can APOE simultaneously protect and impair neural circuits? Here, we dissociated the role of APOE in AD versus aging to determine its effects on neuronal function and synaptic integrity. Using two-photon calcium imaging in awake mice to record visually evoked responses, we found that genetic removal of APOE improved neuronal responses in adult APP/PSEN1 mice (8-10 mo). These animals also exhibited fewer neuritic plaques with less surrounding synapse loss, fewer neuritic dystrophies, and reactive glia. Surprisingly, the lack of APOE in aged mice (18-20 mo), even in the absence of amyloid, disrupted visually evoked responses. These results suggest a dissociation in APOE's role in AD versus aging: APOE may be neurotoxic during early stages of amyloid deposition, although being neuroprotective in latter stages of aging.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Apolipoproteínas E / Regeneração / Córtex Visual / Envelhecimento Limite: Animals / Humans Idioma: En Revista: Life Sci Alliance Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Apolipoproteínas E / Regeneração / Córtex Visual / Envelhecimento Limite: Animals / Humans Idioma: En Revista: Life Sci Alliance Ano de publicação: 2019 Tipo de documento: Article País de afiliação: Estados Unidos País de publicação: Estados Unidos